Abstract: Proxies are mathematical calculations based on fasting glucose and/or insulin concentrations developed to allow prediction of insulin sensitivity (IS) and β-cell response. These proxies have not been evaluated in horses with insulin dysregulation. The first objective of this study was to evaluate how fasting insulin (FI) and proxies for IS (1/Insulin, reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI)) and β-cell response (the modified insulin-to-glucose ratio (MIRG) and the homeostatic model assessment of β-cell function (HOMA-β)) were correlated to measures of IS (M index) using the euglycemic hyperinsulinemic clamp (EHC) in horses with insulin resistance (IR) and normal IS. A second objective was to evaluate the repeatability of FI and proxies in horses based on sampling on consecutive days. The last objective was to investigate the most appropriate cut-off value for the proxies and FI. Results: Thirty-four horses were categorized as IR and 26 as IS based on the M index. The proxies and FI had coefficients of variation (CVs) ≤ 25.3 % and very good reliability (intraclass correlation coefficients ≥ 0.89). All proxies and FI were good predictors of the M index (r = 0.76-0.85; P < 0.001). The proxies for IS had a positive linear relationship with the M index whereas proxies for β-cell response and FI had an inverse relationship with the M index. Cut-off values to distinguish horses with IR from horses with normal IS based on the M index were established for all proxies and FI using receiver operating characteristic curves, with sensitivity between 79 % and 91 % and specificity between 85 % and 96 %. The cut-off values to predict IR were < 0.32 (RISQI), 9.5 µIU/mL for FI. Conclusions: All proxies and FI provided repeatable estimates of horses' IS. However, there is no advantage of using proxies instead of FI to estimate IR in the horse. Due to the heteroscedasticity of the data, proxies and FI in general are more suitable for epidemiological studies and larger clinical studies than as a diagnostic tool for measurement of IR in individual horses.
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The research evaluates different mathematical predictions of insulin sensitivity in horses and demonstrates their effectiveness and consistency, concluding that fasting insulin is an adequately predictive tool.
Objectives and Approach
The main goal of this research was to understand how different proxy measurements (mathematical estimations) for insulin sensitivity (IS) and β-cell response, such as the reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI), correspond to actual measures of IS in horses with insulin resistance (IR) and normal insulin sensitivity.
A secondary goal was to gauge the repeatability of these mathematical measures through day-to-day testing.
The research also aimed to establish optimal cut-off values for these proxies and fasting insulin (FI), enabling better discrimination between horses with IR and those with normal IS.
Findings
The study found that all tested proxies and FI demonstrated significantly high reliability (intraclass correlation coefficients ≥ 0.89) and low variation (coefficients of variation ≤ 25.3 %).
The proxies for IS had a direct relationship with the M index (a measure of insulin sensitivity), while proxies for β-cell response and FI showed an inverse relationship. This indicates they are suitable predictors of insulin resistance and sensitivity.
Researchers established cut-off values for all proxies and FI, distinguishing horses with IR from horses with normal IS, with sensitivities ranging between 79% and 91%, and specificities between 85% and 96%.
Implications
The research concluded that while these proxies reliably estimated a horse’s IS, using proxies doesn’t provide any significant advantage over tracking fasting insulin to estimate insulin resistance in horses.
The authors note that due to the heteroscedasticity (unequal variability) of the data, these proxies and FI tests are more suitable for epidemiological studies or larger clinical experiments as opposed to assessing insulin resistance on an individual horse level.
Cite This Article
APA
Lindåse S, Nostell K, Bergsten P, Forslund A, Bröjer J.
(2021).
Evaluation of fasting plasma insulin and proxy measurements to assess insulin sensitivity in horses.
BMC Vet Res, 17(1), 78.
https://doi.org/10.1186/s12917-021-02781-5
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07, Uppsala, Sweden. sanna.lindase@slu.se.
Nostell, Katarina
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07, Uppsala, Sweden.
Bergsten, Peter
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Forslund, Anders
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Bröjer, Johan
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07, Uppsala, Sweden.
MeSH Terms
Animals
Female
Glucose Clamp Technique / veterinary
Horse Diseases / blood
Horse Diseases / metabolism
Horses
Insulin / blood
Insulin Resistance
Insulin-Secreting Cells / physiology
Male
Conflict of Interest Statement
None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the article.
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